GUT MICROBIOTA IN PRIMARY SCLEROSING CHOLANGITIS: FROM PROGNOSTIC ROLE TO THERAPEUTIC IMPLICATIONS.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acids metabolism, inflammation and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way. SUMMARY: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons. KEY MESSAGES: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role, and the therapeutic implications.

Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.

Prothrombin time predicts steroid response in severe alcohol-related hepatitis.

BACKGROUND AND AIMS: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH). METHODS: Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7. RESULTS: A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954). CONCLUSIONS: BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.

Gut Microbiota and Infectious Complications in Advanced Chronic Liver Disease: Focus on Spontaneous Bacterial Peritonitis.

Liver cirrhosis is a chronic disease that can be complicated by episodes of decompensation such as variceal bleeding, hepatic encephalopathy, ascites, and jaundice, with subsequent increased mortality. Infections are also among the most common complications in cirrhotic patients, mostly due to a defect in immunosurveillance. Among them, one of the most frequent is spontaneous bacterial peritonitis (SBP), defined as the primary infection of ascitic fluid without other abdominal foci. SBP is mainly induced by Gram-negative bacteria living in the intestinal tract, and translocating through the intestinal barrier, which in cirrhotic patients is defective and more permeable. Moreover, in cirrhotic patients, the intestinal microbiota shows an altered composition, poor in beneficial elements and enriched in potentially pathogenic ones. This condition further promotes the development of leaky gut and increases the risk of SBP. The first-line treatment of SBP is antibiotic therapy; however, the antibiotics used have a broad spectrum of action and may adversely affect the composition of the gut microbiota, worsening dysbiosis. For this reason, the future goal is to use new therapeutic agents that act primarily on the gut microbiota, selectively modulating it, or on the intestinal barrier, reducing its permeability. In this review, we aim to describe the reciprocal relationship between gut microbiota and SBP, focusing on pathogenetic aspects but also on new future therapies.

Hospital Services to Improve Nutritional Intake and Reduce Food Waste: A Systematic Review.

BACKGROUND AND AIMS: Patients' nutritional intake is a crucial issue in modern hospitals, where the high prevalence of disease-related malnutrition may worsen clinical outcomes. On the other hand, food waste raises concerns in terms of sustainability and environmental burden. We conducted a systematic review to ascertain which hospital services could overcome both issues. METHODS: A systematic literature search following PRISMA guidelines was conducted across MEDLINE, Web of Science, and Scopus for randomised controlled trials (RCTs) and observational studies comparing the effect of hospital strategies on energy intake, protein intake, and plate/food waste. The quality of included studies was assessed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane Risk of Bias tool from the Cochrane Handbook for Systematic Reviews of Interventions for RCTs. RESULTS: Nineteen studies were included, assessing as many hospital strategies such as food service systems-including catering and room service-(n = 9), protected mealtimes and volunteer feeding assistance (n = 4), food presentation strategies (n = 3), nutritional counseling and education (n = 2), plant-based proteins meal (n = 1). Given the heterogeneity of the included studies, the results were narratively analysed. CONCLUSIONS: Although the results should be confirmed by prospective and large sample-size studies, the personalisation of the meal and efficient room service may improve nutritional intake while decreasing food waste. Clinical nutritionist staff-especially dietitians-may increase food intake reducing food waste through active monitoring of the patients' nutritional needs.

Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives.

The treatment perspectives of advanced hepatocellular carcinoma (HCC) have deeply changed after the introduction of immunotherapy. The results in responders show improved survival compared with Sorafenib, but only one-third of patients achieve a significant benefit from treatment. As the tumor microenvironment exerts a central role in shaping the response to immunotherapy, the future goal of HCC treatment should be to identify a proxy of the hepatic tissue condition that is easy to use in clinical practice. Therefore, the search for biomarkers that are accurate in predicting prognosis will be the hot topic in the therapeutic management of HCC in the near future. Understanding the mechanisms of resistance to immunotherapy may expand the patient population that will benefit from it, and help researchers to find new combination regimens to improve patients' outcomes. In this review, we describe the current knowledge on the prognostic non-invasive biomarkers related to treatment with immune checkpoint inhibitors, focusing on serological markers and gut microbiota.